DNA is continuously exposed to endogenous and exogenous agents that form DNA adducts, which can promote mutagenesis and carcinogenesis. This dissertation examined the mutagenicity and replication bypass of site‑specifically introduced DNA adducts derived from butadiene, vinyl chloride, 4‑hydroxynonenal, and crotonaldehyde. Using mammalian single‑stranded shuttle vectors, these lesions were shown to induce error‑prone replication with lesion‑specific mutation frequencies. Butadiene‑derived N3‑deoxyuridine adducts were the most mutagenic and required translesional synthesis by polymerases η and ζ for efficient bypass. Collectively, these findings elucidate mechanisms by which structurally distinct DNA adducts contribute to mutagenesis in mammalian cells.
